Effect of dapagliflozin on collectins and complement activation in plasma from patients with type 2 diabetes and albuminuria: Data from the DapKid cohort

•What was known:SGLT-2 inhibitors reduce negative kidney and cardiovascular outcomes in patients with diabetes and chronic kidney disease. The effect is not fully accounted for by modest effects on blood pressure, extracellular volume, and a paradox decrease in GFR. Significant anti-inflammatory effects have been demonstrated but the target for the anti-inflammatory effect remains unclear.•This study adds: The study shows that SGLT-2 inhibition with dapagliflozin does not lower plasma concentration of pattern-recognition collectins and complement activation split products in plasma from patients suffering from type 2 diabetes mellitus with clinical albuminuria treated for 12 weeks with dapagliflozin versus placebo. Systemic anti-inflammatory actions of SGLT-2 inhibitors do not include effects on lectin pathway molecules and complement activation.•Potential impact: Potential effects of SGLT-2 inhibitors on complement activation cannot be excluded but are likely local and organ-specific and not reflected in systemic circulating levels. Sodium-glucose cotransporter 2 (SGLT- 2) inhibitors exert cardiovascular and kidney-protective effects in people with diabetes. Attenuation of inflammation could be important for systemic protection. The lectin pathway of complement system activation is linked to diabetic nephropathy. We hypothesized that SGLT-2 inhibitors lower the circulating level of pattern-recognition molecules of the lectin cascade and attenuate systemic complement activation. Analysis of paired plasma samples from the DapKid crossover intervention study where patients with type 2 diabetes mellitus (T2DM) and albuminuria were treated with dapagliflozin and placebo for 12 weeks (10 mg/day, n=36). ELISA was used to determine concentrations of collectin kidney 1 (CL-K1), collectin liver 1 (CL-L1), mannose-binding lectin (MBL), MBL-associated serine protease 2 (MASP-2), the anaphylatoxin complement factor 3a (C3a), the stable C3 split product C3dg and the membrane attack complex (sC5b-9). As published before, dapagliflozin treatment lowered Hba1C from 74 (14.9) mmol/mol to 66 (13.9) mmol/mol (p